dHMN-COQ7

COQ7 | 2023

What Is dHMN-COQ7?

dHMN-COQ7 is a type of CMT caused by autosomal recessive mutations in the COQ7 gene. This gene provides instructions for making an enzyme required for the production of coenzyme Q10, a molecule essential to cellular energy metabolism. Mutations in the COQ7 gene disrupt this function, leading to impaired nerve signal transmission.

dHMN-COQ7 is autosomal recessive, meaning that both copies of the gene must have a mutation to cause this subtype.

Clinical Features

The age of symptom onset in dHMN-COQ7 is variable, ranging from childhood to adulthood. As a motor neuropathy, dHMN-COQ7 primarily affects the most distal points, with weakness and atrophy of the feet and hands, and little to no involvement of the sensory nerves. Nerve conduction studies usually show somewhat slowed conduction velocities and reduced amplitudes, consistent with an axonal form of CMT.

dHMN-COQ7 symptoms may include:

  • Weakness and atrophy in the feet and lower legs
  • Foot drop
  • Reduced or absent reflexes
  • A steppage-style walking pattern
  • Foot deformities, including high arches, and hammertoes (clawed toes)
  • Progressive involvement of the hands
  • Difficulty with fine motor skills and manual dexterity
  • Additional symptoms not listed here

Disease Course

dHMN-COQ7 shows wide variability in severity and progression. Some individuals are mildly affected, while others develop a more severe disease. Disease progression is generally slow, and life expectancy is not reduced.

Clinical Basics

Subtype
dHMN-COQ7

Classification
dHMN/HMN

Subtype Alias
HMNR9

Neuropathy Type
Axonal

Inheritance Pattern
autosomal recessive

Genetic Context

HGNC-Approved Gene Symbol
COQ7

Gene Full Name
coenzyme Q7, hydroxylase

HGNC Gene Alias(es)
CLK1

Chromosome
16p12.3

Zygosity of Responsible Variant
Homozygous or Compound Heterozygous

Mitochondrial Involvement
Yes

Variant Mechanism

Loss of Function (LoF)

Details

Mechanistic basis:
Hypomorphic

Confidence:
High

Prediction:
Hypomorphic COQ7 alleles are predicted by the literature to act through biallelic loss of function in dHMN-COQ7: COQ7 hydroxylates demethoxyubiquinone in the closing steps of coenzyme Q10 synthesis, so when both copies are impaired DMQ10 accumulates while CoQ10 falls, starving motor axons of mitochondrial electron transport. Patient cells treated with 2,4-dihydroxybenzoate, which bypasses the missing hydroxylation step, recover CoQ10, and that biochemical correction is a direct test of the deficit.

Rationale:
A missing enzymatic step, visible as DMQ10 buildup alongside reduced CoQ10, defines this subtype, and metabolite bypass corrects the deficiency in patient fibroblasts. Correction by a downstream intermediate is possible only if the pathology is insufficient product, not a harmful mutant enzyme.

ClinVar Pathogenic Variants

View COQ7 ClinVar Variants

dHMN-COQ7 OMIM Entry

dHMN-COQ7 OMIM

COQ7 OMIM Entry

COQ7 OMIM

More Info

dHMN-COQ7 Research Opportunity

CMT Natural History Study

Original Discovery Publication

Publication Title

Biallelic Variants in COQ7 Cause Distal Hereditary Motor Neuropathy with Uupper Motor Neuron Signs

Authors

Rebelo, A. P., Tomaselli, P. J., Medina, J., Wang, Y., Dohrn, M. F., Nyvltova, E., Danzi, M. C., Garrett, M., Smith, S. E., Pestronk, A., Li, C., Ruiz, A., Jacobs, E., Feely, S. M. E., França, M. C., Gomes, M. V., Santos, D. F., Kumar, S., Lombard, D. B., Saporta, M., Hekimi, S., Barrientos, A., Weihl, C., Shy, M.E., Marques, W., Zuchner, S.

Publication Date
October 1, 2023

Updated: July 18, 2026 | By: K. Raymond

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